Optical scanning devices that operate based on electromagnetic radiation or visible light may be used for scanning material, tissue, or substance properties, for example, surface properties, roughness, absorption behavior, transparency, optical characteristics not perceptible or barely perceptible to the human eye, fractures, cracks, or material deposits.
Medical diagnostics optical scanning devices based on visible light and additional light of an infrared or other suitable wavelength may be used to scan human or animal tissue. The optical light-based scan allows an optical image to be reconstructed and visualized, whereas scanning based on infrared or other suitable light makes it possible, for example, to examine tissue, which is treated beforehand with markers, for the presence of diseases such as cancer. Marked diseased tissue shows fluorescence occurrences in such cases. The method is also referred to as fluorescence scan or fluorescence detection. The scanned image that is created is referred to as a fluorescence scan or fluorescence image.
In addition to the fluorescence characteristics, luminescence characteristics or further optical emission occurrences can also be detected in the same manner. In the following description, the term fluorescence will be used, but may include the further luminescence or emission occurrences in each case.
An apparatus for fluorescence detection, which may be referred to as a fluorescence scanner, can be used to detect a wide range of molecular characteristics because substances with different molecular characteristics exhibit different fluorescence characteristics, which can be explicitly detected. Fluorescence detection is optically based and is non-invasive or is only minimally invasive.
Fluorescence methods are used for examinations of areas close to the surface of the body or examinations of the body opened during an operation (intraoperative applications). Examples of such examinations are the detection of fluorescently marked skin cancer or the detection of tumor boundaries in the resection of fluorescently marked tumors. The company NOVADAQ has developed a system to make intraoperative coronary arteries and the function (i.e. the throughflow) of bypasses visible.
Medical diagnosis molecular characteristics commonly referred to as a “molecular signature,” for example, give information about the state of health of a living thing or patient. The molecular signature may be evaluated diagnostically. Molecular signatures may be employed for the detection of cancer. The molecular signature can also be used to identify other symptoms, such as rheumatoid arthritis or arteriosclerosis of the carotic artery.
Generally, fluorescence detection requires that the fluorescence be excited, which can be done in a simple manner by optical excitation. The excitation light can lie in the infrared range (IR) or in the near infrared range (NIR). A suitable frequency range depends on the substance to be examined. Substances that do not themselves have any molecular or chemical characteristics, which would be suitable for fluorescence detection, can be molecularly “marked” in a suitable manner. For example, markers can be used that, with appropriate preparation, bind or attach themselves to specific molecules. This type of marking functions according to a mechanism which can be illustrated as a key-lock mechanism.
In key-lock mechanisms, markers and molecules to be verified fit into each other like a key in a lock. The marker does not bind to other substances. If the marker exhibits known fluorescence characteristics, it can be optically detected after binding or attachment. The detection of the marker allows the presence of the marked specific substance to be confirmed. Detection only requires one image detector, which is capable of detecting the light in that wavelength that the substance or the marker used emits on excitation.
Fluorescent metabolic markers, which accumulate exclusively in specific regions (e.g. tumors, inflammations or other specific seats of disease) or are distributed throughout the body but are only activated in particular regions, for example, by tumor-specific enzyme activities (and through additional irradiation by light for example), are an object of research in biotechnology.
What are referred to as fluorophores are known as marker substances, for example, indocianine green (ICG). The marker substances, for example, bind to vessels and are optically verifiable. In an imaging method, the contrast with which vessels are displayed can be increased. “Smart contrast agents” are becoming increasingly important. Smart contrast agents are activatable fluorescence markers that, for example, bind to tumor tissue and the fluorescent characteristics that are only activated by binding to the material to be marked. These types of substance may include self-quenched dye media, for example, Cy5.5, which are bound to larger molecules via specific peptides. The peptides can be detected and split up by specific proteases, which are produced in tumors, for example. The splitting up releases the fluorophores and they are then no longer self-quenched but develop their fluorescent characteristics. The released fluorophores can, for example, be activated in the near IR wavelength range around 740 nm. One example of a marker on this basis is AF 750 (Alexa Fluor 750) with a defined absorption and emission spectrum in the wavelength range of 750 nm (excitation) or 780 nm (emission).
In medical diagnosis these types of activatable markers may be used, for example, for intraoperative detection of tumor tissue to enable the diseased tissue to be identified and then removed. A typical application is the surgical treatment of ovarian cancer. The diseased tissue may be surgically removed and subsequently treated using chemotherapy. The increased sensitivity of fluorescence detection increases the ability to detect the diseased tissue along with various surrounding foci of disease and remove the disease more completely.
The detection of a fluorescently marked region includes irradiating the region with the light in the specific excitation wavelength of the fluorescence dye and detecting the emitted light in the corresponding emission wavelength of the fluorophore. A fluorescence scan is created by recording a fluorescence image based on fluorescent light.
If the fluorescence exhibits a low luminous intensity or lies in a wavelength range not visible to the human eye, an additional visualization of the fluorescent tissue areas is necessary. An optical image based on visible light is recorded. Optical and fluorescence image are reproduced superimposed (fused) in order to display the fluorescence within the context of the optical image. The fused image with the fluorescently marked tissue is displayed on a screen of the fluorescence scanner or at an external computer with image processing software.
Users are enabled by the shared reproduction of the optical and the scanning information to orient themselves initially, as regards proportion and position, to the optically reproduced body or object in the display and then transfer the scan information to the real scenario. The surgeon can, for example, detect the tumor tissue on the screen and subsequently locate the tumor tissue in the body of the patient.
To record both an optical and a fluorescence image, a beam splitter may be provided. The beam splitter splits the beam of light coming from the object or body to be examined into a beam that has a spectrum that lies in the wavelength range of the fluorescence and a further beam in the visible wavelength range. The IR or NIR beam is guided to an image detector provided especially for the IR or NIR beam, and the visible beam is guided to a suitable image detector.
Instead of the above splitter, a filter changer can also be arranged in the path of the beam in front of the image detector. The filter changer swaps in a separate filter in each case for recording fluorescence images and for recording optical images. A filter, which filters out the light in the visible wavelength range, must at least be provided for the fluorescence images, since otherwise the fluorescent light would be outshone.
The fluorescent light may lie in the infrared wavelength (IR) range or in the near infrared (NIR) range. Excitation light of a suitable wavelength is only able to be produced at sufficient intensity with a comparatively low efficiency using current lighting devices. Because of the low efficiency, the heat generated is generally large and the energy expended to create the excitation light is considerable.
To reduce heat generation and energy outlay, operation of the fluorescence scanner in an automatically pulsed mode is known. The pulsed mode records images in rapid succession based on visible light and based on fluorescent light.
A shutter with a large aperture is generally provided in the optics of the fluorescent scanner to increase the light sensitivity because of the low luminous intensity of fluorescent light. Although the large aperture increases the light sensitivity, the depth of field obtainable (that is the focal distance range within which it is possible to record an image in sharp focus) is reduced. The fluorescence scanner must be held exactly at a distance from the surface dictated by the focal distance (that is the respective distance which, if maintained, enables the greatest sharpness of the image) to enable an image with the greatest possible sharpness to be recorded.
If a therapeutic intervention based on a scan image is to be planned, a high image quality and resolution are indispensable. If such procedures involve medical intervention on living tissue, an additional factor rendering this situation more difficult can be the tissue's own movement.